Novel extracorporeal procedures are constantly being developed and evaluated for use in patients with sepsis. Preclinical evaluation of such procedures usually requires testing in large animal models. In the present work, the safety and efficacy of a recently developed ADVanced Organ Support (ADVOS) system in a newly developed large animal two-hit model of liver failure combined with endotoxemia were tested.
After establishing the model in more than 50 animals, a randomized study was performed. An inflammatory cholestatic liver injury was initially provoked in pigs. Three days after surgery, endotoxin was gradually administered during 7½ h. Animals were randomized to receive standard medical treatment either with (ADVOS group, n = 5) or without ADVOS (control group, n = 5). The ADVOS treatment was started 2½ h after endotoxemia and continued for 7 h. Survival, cardiovascular, respiratory, renal, liver, coagulation, and cerebral parameters were analyzed.
Three days after surgery, cholestatic injury resulted in hyperbilirubinemia [5.0 mg/dl (IQR 4.3-5.9 mg/dl)], hyperammonemia [292 μg/dl (IQR 291-296 μg/dl)], leukocytosis [20.2 10(3)/μl (IQR 17.7-21.8 10(3)/μl)], and hyperfibrinogenemia [713 mg/dl (IQR 654-803 mg/dl)]. After endotoxemia, the ADVOS procedure stabilized cardiovascular, respiratory, and renal parameters and eliminated surrogate markers as bilirubin [2.3 (IQR 2.3-3.0) vs. 5.5 (IQR 4.6-5.6) mg/dl, p = 0.001] and creatinine [1.4 (IQR 1.1-1.7) vs. 2.3 (IQR 2.1-3.1) mg/dl, p = 0.01]. Mortality: All animals in the ADVOS group survived, while all animals in the control group expired during the 10-h observation period (p = 0.002). No adverse events related to the procedure were observed.
The ADVOS procedure showed a promising safety and efficacy profile and improved survival in a sepsis-like animal model with dysfunction of multiple organs. An amelioration of major organ functions (heart and lung) combined with removal of markers for kidney and liver function was observed.
Pharmacology, Toxicology and Pharmaceutical Science
1
5%
Other
3
14%
Unknown
7
33%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 August 2017.
All research outputs
#7,601,781
of 28,561,469 outputs
Outputs from Intensive Care Medicine Experimental
#212
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Outputs of similar age
#98,887
of 334,912 outputs
Outputs of similar age from Intensive Care Medicine Experimental
#6
of 10 outputs
Altmetric has tracked 28,561,469 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 630 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one has gotten more attention than average, scoring higher than 66% of its peers.
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